The aim of these investigations is to employ immunologic methods to characterize the surface structures of human leukemic cells with the goals of increasing our understanding of the pathophysiology of the malignant process and of establishing a basis for the rational design of specific therapies. Employing the somatic cell hybridization technique, we have prepared potent monoclonal antibodies to the previously described common acute lymphoblastic leukemia antigen (CALLA) and to other less well studied leukemia-associated antigens. Using monoclonal antibodies to CALLA to facilitate identification and isolation of the antigen, we will continue our investigations of this surface glycoprotein as a model for the study of the biological significance and diagnostic and therapeutic utility of other tumor-associated antigens. Specifically, we will study the distribution of CALLA on human and animal tumor cell lines and on cells in tissue sections using the immunofluorescence technique, the immunoperoxidase method, and the immune precipitation procedure. Should significant amounts of CALLA be found on cells of tissues of known function, we will use specific antibody to block or modulate its expression during functional assays of that tissue. In addition, we will search for structural or biochemical changes induced in adherent and suspension target cell populations by modulation of CALLA, assess the normal surface turnover and disposition of CALLA relative to other surface glycoproteins, and isolate and phenotype CALLA positive cells in normal bone marrow in an effort to explain the increased expression of CALLA on malignant versus normal lymphoid cells. These and related studies should also allow us to assess the feasibility of employing antibodies to tumor or tissue-associated antigens as therapeutic agents for the elimination of selective cell populations in vivo (via passive serotherapy) or in vitro (using antibody-treated bone marrow for autologous transplantation). Based on these investigations, we will explore the development of potent drug-antibody conjugates to achieve the selective killing of specific target cell populations.